Fan Shanshan, Su Guangpu, Li Mingfeng, Guo Yunmiao, Wang Lei, Li Jinliang
Clinical Medical Research Institute of Zhanjiang City, Central People's Hospital of Zhanjiang, Zhanjiang 524045, Guangdong, China.
Department of Infectious Diseases, Central People's Hospital of Zhanjiang, Zhanjiang 524045, Guangdong, China.
Mol Genet Metab Rep. 2025 Mar 3;43:101203. doi: 10.1016/j.ymgmr.2025.101203. eCollection 2025 Jun.
Tropomyosin 3 () encodes the slow α-tropomyosin isoform (Tpm3.12), an actin-binding protein that plays a critical role in the regulation of muscle contraction. Mutations in are associated with the characteristic features of congenital myopathy (CM). A 15-year-old boy had a history of developmental delay, he had long narrow face with a myopathic facial appearance, mild scoliosis of the spine, grade IV muscle strength in the extremities, low muscle tone, absent bilateral knee tendon reflexes, and negative pathological findings. MRI revealed fat infiltration in the leg muscles and the surrounding muscle spaces. Muscle biopsy indicated muscle fiber type disproportion. A novel heterozygous mutation of unknown significance, c.44A > G(p.Asp15Gly), in gene was identified. This mutation was confirmed to be de novo and was not present in the proband's parents or sister. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic. PyMOL software analysis indicated that the variant affects the intermolecular interactions within the Tpm3.12. Interestingly, we also found that the patient has been mouth-breathing since infancy, along with a skeletal open bite. This phenotype that has not been previously described. Our study expands the mutation spectrum of and offers valuable insights for the clinical diagnosis and genetic counseling of children with CMYP4A.
原肌球蛋白3（）编码慢α-原肌球蛋白同工型（Tpm3.12），一种肌动蛋白结合蛋白，在肌肉收缩调节中起关键作用。中的突变与先天性肌病（CM）的特征相关。一名15岁男孩有发育迟缓病史，长脸窄，有肌病面容，脊柱轻度侧弯，四肢肌力IV级，肌张力低，双侧膝腱反射消失，病理检查结果为阴性。MRI显示腿部肌肉和周围肌肉间隙有脂肪浸润。肌肉活检提示肌纤维类型不均衡。在基因中鉴定出一个意义不明的新型杂合突变，c.44A>G（p.Asp15Gly）。该突变经证实为新发突变，在先证者的父母或姐妹中不存在。根据美国医学遗传学与基因组学学会（ACMG）的指南，该变异被分类为致病性变异。PyMOL软件分析表明该变异影响Tpm3.12内的分子间相互作用。有趣的是，我们还发现该患者自婴儿期起就一直张口呼吸，伴有骨性开牙合。这种表型此前未见报道。我们的研究扩展了的突变谱，为CMYP4A患儿的临床诊断和遗传咨询提供了有价值的见解。
